Pathophysiology of Kernicterus

Hansen, Thor Willy Ruud

doi:10.1016/b978-0-323-35214-7.00164-5

Cited by 1 publication

(2 citation statements)

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“…It is intriguing that the function and regulation of NCoR1 appears dependent on phosphorylation events (347,490). Bilirubin has previously been shown to inhibit phosphorylation of several proteins/peptides (292,296,297,305) although its interaction with NCoR1 appears not to have been studied specifically. Thus, several processes in bowel homeostasis appear to be linked, contributing to control of the developmental repression of UGT1A1 and to the modulation of hyperbilirubinemia (144).…”

Section: Metabolism Of Bilirubin In the Intestinementioning

confidence: 99%

“…The genetics of hepatic processing and excretion of bilirubin as well as the molecular mechanisms of intestinal handling, may hold the keys to predicting an infant's risk for developing significant NNJ (420,689,692,732). There are many theories that attempt to explain the mechanisms for bilirubin entry into and processing by the brain, the differential sensitivity to bilirubin neurotoxicity both on the individual and cellular levels, and the 'basic mechanism of bilirubin neurotoxicity', if indeed there is only one (305). Neuroprotection has in recent years been developed for asphyxia-related brain damage in the newborn and may be a promising area for NNJ research.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Physiology and Pathophysiology of Bilirubin Handling by the Blood, Liver, Intestine, and Brain in the Newborn

Hansen

Wong

Stevenson

2020

Physiological Reviews

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Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.

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